Alosetron Hydrochloride

This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition

Issued and maintained by the United States Pharmacopeial Convention (USP)

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C₁₇H₁₈N₄O·HCI 330.82

1H-Pyrido[4,3-b]indol-1-one, 2,3,4,5-tetrahydro-5-methyl-2-[(5-methyl-1H-imidazol-4-yl)methyl]-, hydrochloride; 2,3,4,5-Tetrahydro-5-methyl-2-[(5-methylimidazol-4-yl)methyl]-1H-pyrido[4,3-b]indol-1-one hydrochloride CAS RN^®: 122852-69-1.

1 DEFINITION

Alosetron Hydrochloride contains NLT 98.0% and NMT 102.0% of alosetron hydrochloride (C₁₇H₁₈N₄O·HCI), calculated on the anhydrous basis.

2 IDENTIFICATION

Change to read:

A. SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy: 197A OR 197K (CN 1-MAY-2020) Meets the requirements

B. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

C. IDENTIFICATION TESTS-GENERAL (191), Chloride: Meets the requirements of the silver nitrate precipitation test

3 ASSAY

3.1 PROCEDURE

Protect solutions containing alosetron hydrochloride from light.

Buffer: 0.02 M monobasic sodium phosphate. Adjust with phosphoric acid to a pH of 3.0.

Mobile phase: Buffer and acetonitrile (80:20)

Standard solution: 0.05 mg/mL of USP Alosetron Hydrochloride RS in Mobile phase

Sample solution: 0.05 mg/mL of Alosetron Hydrochloride in Mobile phase

Chromatographic system

(See Chromatography (621), System Suitability.).

Mode: LC

Detector: UV 220 nm

Column: 4.6-mm × 7.5-cm; 3-µm packing L1

Flow rate: 1.0 mL/min

Injection volume: 5 µL

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 0.73%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of alosetron hydrochloride (C₁₇H₁₈N₄O·HCI) in the portion of Alosetron Hydrochloride taken:

Result = (r_U/r_S) x (C_S/C_U) x 100

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution

C_S =concentration of USP Alosetron Hydrochloride RS in the Standard solution (mg/mL)

C_U = concentration of Alosetron Hydrochloride in the Sample solution (mg/mL)

Acceptance criteria: 98.0%-102.0% on the anhydrous basis

4 IMPURITIES

4.1 RESIDUE ON IGNITION (281)

NMT 0.2%

Change to read:

4.2 ORGANIC IMPURITIES

Protect solutions containing alosetron hydrochloride from light.

Buffer and Chromatographic system: Proceed as directed in the Assay.

Solution A: Buffer

Solution B: Acetonitrile

Mobile phase: See Table 1. Return to original conditions and re-equilibrate the system.

Table 1

Diluent: Buffer and acetonitrile (90:10)

System suitability solution: 0.5 mg/mL of USP Alosetron Hydrochloride RS and 0.5 µg/mL of USP Alosetron Related Compound A RS in Diluent

Standard solution: 0.5 µg/mL of USP Alosetron Hydrochloride RS in Diluent

Sensitivity solution: 0.25 µg/mL of USP Alosetron Hydrochloride RS in Diluent from the Standard solution

Sample solution: 500 µg/mL of Alosetron Hydrochloride in Diluent

System suitability

Samples: System suitability solution, Standard solution, and Sensitivity solution

Suitability requirements

Resolution: NLT 3 (ERR 1-May-2020) between alosetron and alosetron related compound A, System suitability solution

Relative standard deviation: NMT 5.0%, Standard solution

Signal-to-noise ratio: NLT 10, Sensitivity solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each individual impurity in the portion of Alosetron Hydrochloride taken:

Result = (r_U/r_S) x (C_S/C_U) x (1/F) x 100

r_U = peak response of each impurity from the Sample solution

r_S = peak response of alosetron from the Standard solution

C_S = concentration of USP Alosetron Hydrochloride RS in the Standard solution (µg/mL)

C_U = concentration of Alosetron Hydrochloride in the Sample solution (µg/mL)

F = relative response factor (see Table 2)

Acceptance criteria: See Table 2.

Table 2

5 SPECIFIC TESTS

WATER DETERMINATION (921), Method I, Method Ia: NMT 1.0%

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in tight containers. Store between 15° and 30°, protected from light.

USP REFERENCE STANDARDS (11).

USP Alosetron Hydrochloride RS

USP Alosetron Related Compound A RS

Dealkyl alosetron;

5-Methyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indol-1-one.

C₁₂H₁₂N₂O 200.24